Analysis of polymorphism at site -174 G/C of interleukin-6 promoter region in multiple myeloma

It is well established that interleukin-6 (IL-6) is an essential growth factor for multiple myeloma (MM) and patients with increased IL-6 levels have a poor prognosis. In healthy subjects, the presence of the C allele at a polymorphic site (-174 G/C) of the IL-6 gene is related to low IL-6 levels. In view of the potential association of this particular polymorphism with IL-6 concentration, and the relevance of IL-6 in MM pathogenesis, the objective of the present study was to investigate the prevalence of IL-6 (-174 G/C) promoter polymorphism and its association with development of MM in Brazilian individuals. We investigated the prevalence of these alleles in 52 patients and 60 healthy subjects (matched by age, sex, and race) of a Brazilian population. Thirty patients were male (42.4 percent), 24 (46.2 percent) were white and the median age at diagnosis was 58.5 years (range: 28 to 84 years). To determine the IL-6 (-174 G/C) polymorphism, molecular analysis was performed by polymerase chain reaction followed by endonuclease restriction digestion. The genotype distributions observed in the group of patients were 4 percent CC, 42 percent GC and 54 percent GG. The C allele frequency was 0.25. These results were similar to the control group, suggesting no impact of this polymorphism on the susceptibility to MM.

Plasmablastic multiple myeloma is associated with increased vascular endothelial growth factor immunoexpression

The biologic basis of the negative prognosis of plasmablastic myeloma is not fully understood. To determine whether histologically aggressive multiple myeloma (MM) is associated with a more angiogenic marrow environment, bone marrow samples from 50 recently diagnosed MM patients were evaluated. Twelve percent (6/50) of patients presented plasmablastic MM, and this feature correlated with moderate/strong intensity of vascular endothelial growth factor staining of plasma cells (P = 0.036). Although plasmablastic MM was not associated with increasing of microvessel density, this new evidence of increased expression of vascular endothelial growth factor on plasmablasts suggests that the adverse prognosis conferred by plasmablastic disease may be due, at least in part, to secretion of this angiogenic cytokine, also suggesting that the subset of MM patients with plasmablastic features may derive particular benefit from antiangiogenic therapies.

Renal dysfunction in patients with sickle cell anemia or sickle cell trait

Patients with sickle cell anemia (Hb SS) or sickle cell trait (Hb AS) may present several types of renal dysfunction; however, comparison of the prevalence of these abnormalities between these two groups and correlation with the duration of disease in a large number of patients have not been thoroughly investigated. In a cross-sectional study using immunoenzymometric assays to measure tubular proteinuria, microalbuminuria, measurement of creatinine clearance, urinary osmolality and analysis of urine sediment, we evaluated glomerular and tubular renal function in 106 adults and children with Hb SS (N = 66) or Hb AS (N = 40) with no renal failure (glomerular filtration rate (GFR)>85 ml/min). The percentage of individuals with microalbuminuria was higher among Hb SS than among Hb AS patients (30 vs 8 per cent, P<0.0001). The prevalence of microhematuria was similar in both groups (26 vs 30 per cent, respectively). Increased urinary levels of retinol-binding protein or ß2-microglobulin were detected in only 3 Hb SS and 2 Hb AS patients. Urinary osmolality was reduced in patients with Hb SS or with Hb AS; however, it was particularly evident in Hb SS patients older than 15 years (median = 393 mOsm/kg, range = 366-469) compared with Hb AS patients (median = 541 mOsm/kg, range = 406-722). Thus, in addition to the frequently reported early reduction of urinary osmolality and increased GFR, nondysmorphic hematuria was found in 26 and 30 per cent of patients with Hb SS or Hb AS, respectively. Microalbuminuria is an important marker of glomerular injury in patients with Hb SS and may also be demonstrated in some Hb AS individuals. Significant proximal tubular dysfunction is not a common feature in Hb SS and Hb AS population at this stage of the disease (i.e., GFR>85 ml/min)

Diagnóstico laboratorial da anemia hemolítica auto-imune: características do teste manual direto do Polybrene / Laboratory diagnosis of auto-immune hemolytic anemia: characteristics of the manual direct test of Polybrene

O teste manual direto do Polybreneâ (TDP) e o teste de Coombs direto (TCD) foram utilizados para a detecçäo de IgG na superfície de hemácias de pacientes com diagnóstico clínico e laboratorial de anemia hemolítica auto-imune (AHAI). Objetivo. Comparar a sensibilidade e especificidade do TPD e do TCD no diagnóstico da AHAI. Método. Foram estudados 18 pacientes com diagnóstico clínico-laboratorial de AHAI. Como indivíduos controles, foram testados 20 doadores de sangue assintomáticos e 20 pacientes com anemia falciforme. Resultados. O TCD foi positivo em 14 pacientes e negativo em quatro indivíduos, enquanto o TDP foi positivo em 17 pacientes e negativo em um indivíduo que apresentava TCD positivo devido a fixaçäo de complemento (C3d) nas hemácias. Todos os eluatos positivos realizados com a técnica de diclorometano revelaram anticorpos quentes com especificidade "anti-Rh". A sensibilidade do TDP (94 por cento) para detectar fixaçäo de IgG in vivo foi significantemente maior (p<0,05) que a do TCD (78 por cento), enquanto os dois testes apresentaram a mesma especificidade (100 por cento). Conclusäo. O presente estudo permite concluir que, além de apresentar maior sensibilidade que o TCD, o TDP é um método rápido e de baixo custo, sendo, dessa forma, um teste auxiliar útil no diagnóstico de AHAI, especialmente nos pacientes com TCD negativo.

Aplicaçäo clínica de filtros leucocitários / Clinical applications of leukocyte filters

A presença de leucócitos nos produtos hemoterápicos alogênicos transfundidos tem sido associada à ocorrência de determinadas reaçöes transfusionais, tais como a reaçäo transfusional febril näo-hemolítica, a aloimunizaçäo e refratariedade à transfusäo de plaquetas, a doença enxerto-versus-hospedeiro, e a efeitos imuno-modulatários. Além disso, os leucócitos podem ser vetores de transmissäo de agentes infecciosos, tais como o CMV, o HTLV-I/II e o EBV. Tem sido postulado que a remoçäo dos leucócitos em hemocomponentes mediante uso de filtros leucocitários pode prevenir a ocorrência dessas reaçöes. Entretanto, a eficácia clínica da desleucotizaçäo permanece sem definiçäo. Tem sido sugerido que a remoçäo de 1 log(10) de leucócitos previne a reaçäo transfusional näo-hemolítica, a remoçäo de 2 log(10) pode prevenir a transmissäo de viroses, enquanto que a remoçäo de maior ou igual 3 log(10) pode ser necessária para a prevençäo de aloimunizaçäo plaquetária. Entretanto, devido à carência de estudos que analisem apropriadamente as vantagens do uso clínico rotineiro dos filtros, permanecem sem completa definiçäo quais säo as reais indicaçöes clínicas para o uso de hemocomponentes desleucotizados; quais säo os graus de desleucotizaçäo necessários para prevenir as diferentes reaçöes; e se a remoçäo dos leucócitos deve ser realizada antes ou após o armazenamento de hemocomponente. Dessa maneira, somente estudos clínicos prospectivos poderäo definir o custo-benefício da aplicaçäo clínica de filtros leucocitários em hemoterapia.

Fetal hemoglobin in patients with chronic renal disease

To investigate whether hemoglobin (Hb) synthesis is affected by different treatment protocols used for end-stage renal disease, we analyzed the electrophoretic pattern of hemoglobin in 136 adult patients with chronic renal failure. Forty-seven patients were not in a dialysis program (ND), 29 individuals were on continuous ambulatory peritoneal dialysis (CAPD), 33 patients were on hemodialysis(HD), and 27 subjects had received a kidney transplant (KT). We found 3.6 per cent hemoglobin C, 1.4 per cent hemoglobin S and 3.6 per cent beta-thalassemia minor as reported in other studies of Brazilian patients. In addition, we found increased fetal hemoglobin (Hb F) levels in 7.4 per cent of the patients which contrasts with the reported 0.01 per cent prevalence rate of hereditary persistence of Hb F in Brazil. Seven out of ten patients with elevated Hb F belonged to either the CAPD or the KT group. We postulate that stress erythropoiesis is probably the mechanism responsible for the Hb F increase in these patients. However, properly designed clinical studies are still necessary to clarify these questions.

Measurement of red blood cell antibodies in autoimmune hemolytic anemia

The enzyme-linked antiglobulin test (ELAT) was employed to measure the number of IgG molecules per red blood cell (IgG/RBC0 in 11 patients with autoimmune hemolytic anemia (AIHA). All patients with AIHA had high levels of red cell-associated IgG (110-3,650IgG/RBC). The control group consisted of normal volunteers (N=10) and patients with hereditary spherocytosis (N=1), ß--thalassemia (N=1), immunologic thrombocytopenic purpura (N=3) and IgG multiple myeloma (N=4). All control individuals presented low levels of red cell IgG (less than 38IgG/RBC) with the exception of one of four patients with myeloma who had a mildly elevated value (50 IgG/RBC). Since the multiple myeloma patients had > 2g/dl IgG, the possible nosnspecific uptake of IgG onto the RBCs of patients with elevated serum IgG values did not interfere with the results of ELAT. ELAT proved to be a useful method for accurate quantification of the amount of IgG specifically bound on the surface of RBC of patients with AIHA

Level of fetal hemoglobin as an indicator of clinical complications in sickle cell anemia

The fetal hemoglobin (HbF) level was used as an indicator of the development of severe clinical complications in 89 patients with sickle cell anemia (SCA). HbF was determined by the alkali denaturation technique. The mean HbF level was 6.7 + or - 4.2% (range, 0.7 to 19.2%) of total hemoglobin. Major organ failures were considered to be teerminal events of morbidity and included 8 cerebrovascular accidents, 13 aseptic necroses of the femoral head and 17 leg ulcer episodes. The characteristics of the test, including sensitivity, specificity and positive predictive value were analyzed for different levels of HbF. The overall specificities were 76,76, and 85% for HbF levels >=8,10 and 12%, respectively. The sensitivity of the test was low. The positive predictive value reached 71% for children with HbF >=8%. The data suggest that HbF level may be a useful indicator of the possibility of a patient developing serious clinical complications